Tocopherol esters and their cosmetic and pharmaceutical uses

ABSTRACT

The invention relates to an ester. The ester is characterized in that it presents the following chemical formula (I): ##STR1## in which: R 1 , R 2  and R 3  independently represent an atom of hydrogen, a methyl radical, 
     A represents the following groups: ##STR2## R 4  and R 5  are identical or different and each represents a chain of the form: 
     
         --B.sub.m --C.sub.n --B.sub.p --C.sub.q --H 
    
     in which: 
     B is the following group: ##STR3## C is the following group: ##STR4## and in which the indices m, n, p, and q are respective integers lying in the range 0 to 4, it being understood that the sum m+n+p+q is limited to integers in the range 0 to 4. 
     The ester can be used for preparing cosmetic or pharmaceutical, in particular dermatological, compositions having activity against radicals, against inflammation, favoring differentiation of keratinocytes, improving skin moisturizing, improving skin grain fineness, and having anti-aging or depigmenting activity.

This application is a 371 of PCT/FR98/00958 filed May 14, 1998.

FIELD OF THE INVENTION

The invention relates by way of novel substance to tocopherol esters, toa use thereof in cosmetics or pharmacy, in particular dermatology, andalso to cosmetic or pharmaceutical, and in particular dermatological,compositions containing them.

SUMMARY OF THE PRIOR ART

It is known that alpha-tocopherol or vitamin E is to be found in thenatural state in numerous plants, usually with other compounds such asbeta-tocopherol, gamma-tocopherol, and delta-tocopherol.

Alpha-tocopherol is essentially used to combat vitamin E deficiencies,or as a nutrient, in particular to combat muscular degeneration.

It is also used as an antioxidizing agent, but in highly specific doses.

SUMMARY OF THE INVENTION

In the context of the present invention, there have been discovered in amanner that is quite surprising and unexpected, both novel esters oftocopherol and the fact that these novel esters of tocopherol presentpowerful activity against radicals, against inflammation, in improvingdifferentiation of keratinocytes, in improving moisturizing of the skin,in improving skin grain fineness, in anti-aging activity, indepigmenting activity, and in anesthetic effects on cutaneous nerveendings.

Thus, the present invention seeks to resolve the novel technical problemconsisting in supplying an active substance having good activity againstradicals, against inflammation, against aging, for depigmenting, forimproving the differentiation of keratinocytes, for moisturizing theskin, for the fineness of skin grains, and also anesthetic action oncutaneous nerve endings, in particular by topical or generalapplication, thus constituting an active ingredient that is valuable inpreparing cosmetic, pharmaceutical, and in particular dermatologicalcompositions.

The present invention resolves this novel technical problem insatisfactory manner using a solution that is particularly simple, andsuitable for use on an industrial scale.

DETAILED DESCRIPTION OF THE INVENTION

Thus, in a first aspect, the present invention covers esters,characterized in that they present the following chemical formula (I):##STR5## in which: R₁, R₂ and R₃ independently represent an atom ofhydrogen, a methyl radical,

A represents the following groups: ##STR6## R₄ and R₅ are identical ordifferent and each represents a chain of the form:

    --B.sub.m --C.sub.n --B.sub.p --C.sub.q --H

in which:

B is the following group: ##STR7## C is the following group: ##STR8##and in which the indices m, n, p, and q are respective integers lying inthe range 0 to 4, it being understood that the sum m+n+p+q is limited tointegers in the range 0 to 4.

In a variant embodiment of the invention, the esters are characterizedin that R₄ and R₅ represent hydrogen.

In a variant embodiment of the invention, the esters are characterizedin that at least one of the groups R₄ and R₅ represents hydrogen.

In a variant embodiment of the invention, the esters are characterizedin that one of the groups R₄ or R₅ represents hydrogen, and the other a2,5-dihydroxybenzoyl radical.

In a variant embodiment of the invention, the esters are characterizedin that they are selected from the group consisting in esters ofalpha-tocopherol, of beta-tocopherol, of gamma-tocopherol, of zeta1-tocopherol, of zeta 2-tocopherol, of delta-tocopherol, ofeta-tocopherol, of epsilon-tocopherol, and of tocol.

In a variant embodiment of the invention, it relates to an estersatisfying formula (II) below: ##STR9##

In a variant embodiment of the invention, it relates to an estersatisfying formula (III) below: ##STR10##

Esters of above formulae (II) and (III) are referred to below asalpha-tocopherol 2,5-dihydroxybenzoate diester respectively of formula(II) and of formula (III), or else as "diester A₁ " and "diester A₂ ".

In a second aspect, the present invention also covers a cosmetic orpharmaceutical composition, and in particular a dermatologicalcomposition, characterized in that by way of active ingredient itcomprises at least one ester of formula (I) as defined above.

In a variant embodiment, the said composition is characterized in thatit comprises as active ingredient at least two esters as defined above,in the form of a mixture.

In a variant embodiment, the said composition is characterized in thatthe said ester is present in a fatty phase of said composition.

In another variant embodiment, the said composition is characterized inthat the fatty phase comprises at least one cosmetically orpharmaceutically or dermatologically acceptable oil, in particular anoil selected from the group constituted by jojoba oil, macadamia oil,limnanthes seed oil, in particular from Limnanthes alba benth(Meadowfoam), mineral oils, and triglycerides, in particulartriglycerides based on caprylic acid and/or capric acid, or mixturesthereof.

In a variant embodiment, the said composition is characterized in thatits concentration in said formula I ester lies in the range 0.001% to5%, better in the range 0.01% to 1% by weight relative to the totalweight of the final composition.

In a particular variant embodiment, the said composition ischaracterized in that it comprises as an active ingredient at least onealpha-tocopherol ester corresponding to said chemical formula I, inwhich each of R₁, R₂ and R₃ represents a methyl radical,

A represents the group: ##STR11## and R₄ and R₅ have the values asdefined above.

In another variant embodiment, said composition is characterized in thatit comprises at least one other active ingredient, in particularselected from the group constituted by vitamins A, B1, B6, B12, E, C,PP, retinoic acid, retinal, retinol and esters thereof, salicylic acidand derivatives thereof, in particular salts or esters thereof,2,5-dihydroxybenzoic acid, tocopherol and esters thereof, in particulartocopherol phosphate, asiatic acid, madecassic acid and itsglycoside-containing esters, asiaticoside, an extract of Centellaasiatica, an extract of Siegesbeckia orientalis, proantocyanideoligomers, in particular those obtained from grape pips, and estersthereof, in particular the palmitic and stearic esters, derivatives ofascorbic acid, in particular its phosphate and its salts, erythorbicacid, oligoelements, in particular in the form of a salt, specificallyin the form of an aspartate or a chloride of magnesium, selenium, zinc,or copper, alpha-hydroxylated acids, in particular malic acid, lacticacid, and tartaric acid, and esters thereof, in particular with fattyalcohols, such as stearyl alcohol, amino acids, in particular serine,threonine, citrulline, and amino acids constituting NMF (NaturalMoisturizing Factor: K. Sakamoto, Cosmet. Toilet. (1984) 99 (3)109-117), ceramides, in particular 2, 3 or 6 ceramides used singly or ina mixture, photoceramides, in particular those extracted from wheat, andecdysteroids, in particular ecdysterone, and esters thereof.

In another particular embodiment, said composition is characterized inthat the ester of said formula I is used in combination with vitamin A,preferably in the form of an ester such as palmitate.

In a third aspect, the present invention also covers the use as acosmetic agent of at least one ester of formula I as defined above,advantageously included in the said cosmetic composition.

In the context of its use as a cosmetic agent, the ester of said formula(I) is used to avoid or attenuate the harmful effects of free radicalson the skin, for preventing or treating rashes and sensations of skinprickling or stinging, to favor keratinocyte differentiation, to restorenormal moisturizing of the epidermis, to improve skin grain fineness, toslow down or treat the effects of aging on the skin, such as theappearance of wrinkles or loose skin, and to attenuatehyperpigmentation, in particular pigmented spots due to skin aging.

The harmful effects of free radicals include a particularly damagingeffect due to free radicals constituted by oxygen, namely peroxidyzingcutaneous substances, in particular the membrane lipids of cells such askeratinocytes. These free radicals constituted by oxygen are in everincreasing concentration in polluted atmospheres because of the combinedaction of temperature, sunlight, and industrial pollutants, includingmotor vehicle exhaust gases. These free radicals give rise toaccelerated aging of the skin, and the effects thereof can be preventedor treated or attenuated by using the esters of the present invention.

In a fourth aspect, the invention also covers the use of at least oneester of above-defined formula I for making a pharmaceuticalcomposition, in particular a dermatological composition, having activityagainst radicals, against inflammation, or an anesthetic action oncutaneous nerve endings.

In a variant, said composition comprises 0.001% to 5%, and better 0.01%to 1% by weight of the final composition.

In a fifth aspect, the present invention also covers a cosmetictreatment method characterized in that a cosmetically effective quantityof at least one ester of above-defined formula I is applied topically tothe skin of a human being, in particular in the form of a compositioncontaining the ester of said formula I at a concentration lying in therange 0.001% to 5%, and preferably in the range 0.01% to 1% by weight ofthe final composition.

In a sixth aspect, the present invention also covers a therapeutictreatment method characterized in that a therapeutically effectivequantity of at least one ester of above-defined formula I is appliedtopically to the skin of a human being, in particular in the form of acomposition containing the ester of said formula I at a concentrationlying in the range 0.001% to 5%, and preferably in the range 0.01% to 1%by weight of the final composition. In the context of this therapeuticapplication, the invention makes it possible to obtain activity againstradicals, against inflammation, or anesthetic action on cutaneous nerveendings.

It can be seen from the above description that compositions of theinvention can be formulated in any form that is acceptable for use incosmetics, dermatology, or pharmacy. In particular, it can beconstituted by a cream, a lotion, an emulsion, or indeed a lotion.

The invention is described below in detail with the help of variousexamples given purely by way of illustration and which therefore do notlimit the scope of the invention in any way, and also with reference tothe accompanying sole FIGURE.

DESCRIPTION OF THE SOLE ACCOMPANYING FIGURE

The sole accompanying FIGURE is a graph with hydrogen peroxide (H₂ O₂)concentration as used as a generator of free radicals giving rise tocellular toxicity plotted along the abscissa, which toxicity is possiblycombated by DHBT of the invention at the concentration under test, andwith the percentage of cell viability plotted up the ordinate, asobtained by the neutral red test on normal human keratinocytes or KHn.

In the examples, the percentages are given by weight, the temperaturewas ambient temperature, and the pressure was atmospheric pressure,except where stated otherwise. When temperatures are given, they aregiven in degrees Celsius.

EXAMPLE 1 Synthesizing Esters of 2,5-Dihydroxybenzoic Acid withAlpha-Tocopherol

The reaction is based on causing 2,5-dihydroxybenzoic acid to react withalpha-tocopherol, which leads to esters having said chemical formula Ibeing formed, in which A represents the group: ##STR12## Each of R₁, R₂and R₃. represents a methyl radical; and R₄ and R₅ have theabove-defined values.

More precisely, synthesis of esters was performed as follows:

A 2 liter flask fitted with half-moon stirring, a thermometer, a cooler,and a Dean Starck apparatus was filled with 172.3 g (0.4 moles) ofalpha-tocopherol, 600 g of xylene, and 123.2 g (0.8 moles) of2,5-dihydroxybenzoic acid.

56 g of 96% sulfuric acid was added at 25° C., thereby producing anexothermal reaction.

The resulting liquid was distilled for a duration of about 7 h. It wascooled to 50° C., about 1000 g were emulsified, and then chloroformextraction was performed by adding 2500 g of chloroform.

The organic phase was washed with 500 g of 2% aqueous solution of sodiumcarbonate and with 1500 g of water. The mixture was allowed to settleand the aqueous phase separated out.

The chloroform-based organic phase was distilled and 203.4 g ofalpha-tocopherol esters were obtained with a yield of 89%. Thealpha-tocopherol esters were in the form of a dark brown viscous liquid.When assayed using high performance liquid chromatography (HPLC), fromthe area ratios, the liquid comprised 6.3% tocopherol, 49% esters ofalpha-tocopherol 2,5-dihydroxybenzoate, and 34% other substances.

Method of Purification

A 2 liter flask fitted with half-moon stirring, a thermometer, and acooler was filled with 180 g of the viscous liquid containing thealpha-tocopherol 2,5-dihydroxybenzoate esters obtained in the precedingstep, together with 600 g of toluene, and then active carbon in powderform.

After a period of several hours contact with the active carbon, theliquid was clarified by filtering out the active carbon and the toluenewas distilled. This provided 116 g of alpha-tocopherol2,5-dihydroxybenzoate esters. The yield was 64%. The alpha-tocopherol2,5-dihydroxybenzoate esters were in the form of a brown viscous liquid.

Further HPLC analysis gave 10.4% alpha-tocopherol, 54% alpha-tocopherol2,5-dihydroxybenzoate esters, and 31% other substances. This analysisconfirmed that the esters were esters of alpha-tocopherol2,5-dihydroxybenzoate.

It will be observed that this example which is given usingalpha-tocopherol can be implemented without difficulty using othertocopherols.

EXAMPLE 2 Preparing Purified Alpha-Tocopherol 2,5-DihydroxybenzoateMonoester

Alpha-tocopherol 2,5-dihydroxybenzoate monoester can be obtained withgood yield by using the synthesis conditions described in Example 1, butby performing a reaction at a lower temperature, of the order of 40° C.to 60° C. and with a shorter reaction time, in the range 2 h to 4 h.

Under such circumstances, the main reaction product obtained is amixture of alpha-tocopherol 2,5-dihydroxybenzoate diesters and monoesterin the form of a chloroform solution, referred to below as SC. Theseesters can be separated using the following method:

A--Purification of Alpha-Tocopherol 2,5-Dihdroxybenzoate Monoester

From the chloroform solution SC at 100 mg/ml, as obtained above,preparative silica chromatography was carried out, e.g. using a MerckF254 plate, together with a hexane and ethyl acetate mixture (80/20 byvolume) as the eluent system. The fraction followed by UV absorption at320 nm was recovered. It was concentrated and dried. A product having anrf of 0.6 was obtained, constituted by alpha-tocopherol2,5-dihydroxybenzoate monoester.

The alpha-tocopherol 2,5-dihydroxybenzoate monoester was in the form ofa pale beige viscous liquid, that fluoresced under short and long UV,and that was soluble in chloroform and ethanol.

Its empirical chemical formula was C₃₆ H₅₄ O₅ with a molecular weight of566 g.

Its UV spectrum was characterized by the following λ max: 330 nm, 286nm, 277 nm.

By electron impact mass spectrometry (70 eV), the following M⁺characteristic fragments were obtained: 566, 430, 416, 301.

Its developed chemical formula was as follows: ##STR13## B--A Method ofPurifying Alpha-Tocopherol 2,5-Dihydroxybenzoate Diesters

From the said chloroform solution SC at 100 mg/ml, preparative silicachromatography was carried out, e.g. on a Merck F254 plate, using amixture of hexane and ethyl acetate (20/80 by volume) as the eluantsystem. A majority fraction followed by UV absorption at 320 nm wasrecovered and then concentrated and reduced to dryness.

A product having an rf of 0.45 was obtained constituted by a mixture oftwo alpha-tocopherol 2,5-dihydroxybenzoate diesters, namely: the diesterin which the second 2,5-dihydroxybenzoic ester constitutes an orthosubstituent of the first ester, referred to as "diester A₁ " inabove-described formula (II), and the diester in which the second2,5-dihydroxybenzoic ester is a substituent in the meta position of thefirst ester, referred to as "diester A₂ " of above-described formula(III).

The characteristics of the mixture of alpha-tocopherol2,5-dihydroxybenzoic diesters having formulae (II) and (III)respectively are as follows: pale yellow ochre viscous liquid having anrf of 0.45, fluorescent under short and long UV, soluble in chloroformand ethanol. The empirical chemical formula was C₄₃ H₅₈ O₈ with amolecular weight of 702, the UV spectrum presented λ max at 338 nm, 286nm, and 277 nm. Electron impact mass spectrometry (70 eV) gave thefollowing M⁺ characteristic fragments 702, 670, 662, 647, 566, 430, 416,301.

By way of example, the diesters A₁ and A₂ can be separated by subjectingthe raw mixture to chromatography on a C-18 silica plate (F254 fromMERCK®) using an elution solvent under the following conditions:methanol/water/acetic acid/tetrahydrofuran in the following volumeratio: 88.4/7.6/3.92/0.08.

For the purpose of separating these two diesters by industrialpreparative chromatography using a silica column, it is preferable touse as the eluant a 95/5 mixture of hexane and ethyl acetate.

Diester A₁ presents the following relative intensities of fragmentationions close to the molecular ion (702): 702 (10), 670 (70), 662 (14), 647(22).

Diester A₂ presents the following relative intensities of fragmentationions close to the molecular ion (702): 702 (3), 670 (25), 662 (28), 647(48).

EXAMPLE 3 Studying the Protective Effect of Alpha-Tocopherol2,5-Dihydroxybenzoate Esters Against the Cytotoxicity of Free Radicals

1. Principles of the Test

Various concentrations of alpha-tocopherol 2,5-dihydroxybenzoate,hereinafter "DHBT", dissolved in dimethylsulfoxide (DMSO) were tested incultures of normal human keratinocytes (KHn) exposed to variousconcentrations of oxygen containing free radicals produced by hydrogenperoxide (H₂ O₂) present in the culture media.

For each concentration tested, cellular viability was evaluated by theso-called "neutral red" test.

The test essentially comprises comparisons, namely:

reference cultures that do not receive hydrogen peroxide, but that doreceive DHBT dissolved in DMSO like the treated cultures (control);

cultures that do not receive hydrogen peroxide, and that receive onlyDMSO, the solvent of DHBT, in quantities identical to that of thecultures treated by DHBT (DMSO reference).

The tested DHBT dissolved in DMSO was in fact the mixture ofalpha-tocopherol 2,5-dihydroxybenzoate esters obtained in Example 1.

2. Test Protocol

a) Source of the Keratinocytes

Normal human keratinocytes (KHn) that had been taken surgically fromhealthy skins were used.

b) Culture Conditions

The KHn were maintained in complete serum free media (SFM), referred tobelow as SFMc, from Gibco. The cells were successively cultivated seventimes, and on the seventh pass, referenced P7, the KHn cells werecollected.

c) Treatment Conditions

P7 KHn cells were seeded in 96-well culture plates at a rate of 1000 KHnper well in serum free medium, K-SFM medium from Gibco, and treated 24hours later with various concentrations of hydrogen peroxide (H₂ O₂,Sigma, reference H-1009), respectively at 1 μM, 5 μM, 10 μM, 25 μM, 50μM, 75 μM, and 100 μM. For each of these concentrations of H₂ O₂, threeconcentrations of tocopherol gentisate were also tested, respectively at0.1 μg/ml, 1 μg/ml, and 10 μg/ml.

The KHn cells were incubated with the various substances in a HANKSbalanced saline solution (HBSS from Gibco, reference: 14175-053) for onehour at 37° C. After incubation, the cells were rinsed with HBSS buffer,and a neutral red test was performed, constituting a viability test,showing up lysosomial activity.

d) Neutral Red Test

This test consisted in rinsing the cells with Dulbecco phosphate buffer(PBS, from Gibco, reference: 14190).

Thereafter, the cells were incubated for 3 hours at 37° C. with 200 μlper well of neutral red solution (mother solution at 0.4% in water) at1.25% (v/v) in SFMc medium.

Only living cells take on a red color. Consequently, the intensity ofthe red color, measured in terms of optical density, depends directly onthe number of living cells.

After incubation, the cells were rinsed with PBS.

Thereafter, 100 μl were added to each well of a mixture of 50%ethanol+1% acetic acid.

The plate was stirred for 15 minutes.

Thereafter, optical density was measured at 540 nm by spectrophotometry.

Cell viability is expressed in percentage terms, using the followingequation: ##EQU1## in which, for each value of DHBT concentration,DO_(TB) is the optical density of "control" cultures, and DO_(PH) is theoptical density of cultures containing hydrogen peroxide (H₂ O₂).

3. Results

The results obtained are summarized in Table I below.

                                      TABLE I                                     __________________________________________________________________________    Viability (%) of KH.sub.n keratinocytes in culture, in the presence of         alpha-tocopherol 2,5-dihydroxybenzoate (DHBT) and oxygen-containing free     radicals                                                                              NO     DHBT    DHBT    DHBT                                                                                DHBT  0.1 μg/ml  1 μg/ml  10                                           μg/ml                                    Mean σ Mean σ Mean σ Mean σ                         __________________________________________________________________________    Control 100.00                                                                            6.82                                                                             100  2.82                                                                             100  2.45                                                                             100  4.21                                        DMSO reference   107.38** 1.11 103.85** 1.04 105.31** 3                       H.sub.2 O.sub.2 1 μm 108.25 8.13 110.47 3.66 99.88 1.36 103.67 3.66                                           H.sub.2 O.sub.2 5 μm 106.93 6.2                                           109.88 0.45 106.87 0.67 107.67 3.11                                            H.sub.2 O.sub.2 10 μm 109.04 8.44                                         102.85 8.47 103.74 2.26 111.99 2.44                                            H.sub.2 O.sub.2 25 μm 95.16 6.39                                          94.16 20.07 99.21 4.49 112.35 4.59                                             H.sub.2 O.sub.2 50 μm 85.33* 4.74                                         85.1* 2.75 86.52* 4.32 107.04 4.93                                             H.sub.2 O.sub.2 75 μm 72.42* 11.4                                         85.37* 2.65 72.46* 3.32 90.73* 4.41                                            H.sub.2 O.sub.2 100 μm 59.07* 8.9                                         68.4* 4.08 53.04* 6.87 85.71*             __________________________________________________________________________                                        2.43                                       *Results significant at 5% (p < 0.05).                                        **DMSO reference cultures did not receive DHBT, but only DMSO.           

The same results are also plotted as curves in the sole accompanyingFIGURE.

The concentrations of hydrogen peroxide (H₂ O₂) used as a generator offree radicals giving rise to cellular toxicity is plotted along theabscissa, and is possibly combated by the DHBT of the invention at theconcentration under test, while the cell viability percentage is plottedup the ordinate, as obtained by the neutral red test on normal humankeratinocytes or KHn.

The curve interconnecting circles corresponds to cultures containinghydrogen peroxide, but not receiving DHBT; the curve connecting squarescorresponds to cultures receiving DHBT in DMSO of the invention at aconcentration of 0.1 μg/ml of culture; the curve connecting trianglescorresponds to cultures receiving DHBT in DMSO of the invention at aconcentration of 1 μg/ml of culture, and finally the curve connectingcrosses corresponds to cultures receiving DHBT of the invention at aconcentration of 10 μg/ml of culture.

It is recalled that cultures corresponding to the DMSO reference did notreceive DHBT, but only its solvent DMSO.

From Table I, and from the curves plotted in the sole accompanyingFIGURE, it can be seen that hydrogen peroxide is toxic for thekeratinocytes used as from 25 μM, above which the cell viability ratedrops sharply from about 100%.

However, when the cells are treated both with hydrogen peroxide and withDHBT of the invention at a concentration of 10 μg/ml, the toxicity ofthe hydrogen peroxide is not observable until its concentration is 75μM, i.e. until its concentration is three times greater, whichdemonstrates significant resistance of the keratinocytes to attack fromfree radicals, with this being achieved by DHBT at such a concentration.

Thus, this test shows clearly that the antiradical activity isparticularly effective, specifically for making a pharmaceuticalcomposition, in particular a dermatological composition, or a cosmeticcomposition, or as a cosmetic agent.

In addition, given that the oxygen-containing free radicals peroxidizecutaneous lipids, the present invention makes it possible to prevent ortreat effectively the effects of aging on the skin. In particular, thoseeffects which are due to free radicals, and specifically those which aregenerated by atmospheric pollution.

The invention is described below with reference to various examples ofcosmetic or pharmaceutical, in particular dermatological compositionsgiven merely as illustrations and which therefore do not limit the scopeof the invention in any way.

In the examples, concentrations are given in grams.

EXAMPLE 4 Antiwrinkle Cream

    ______________________________________                                        The cream was prepared using the following active ingredients:                ______________________________________                                        purified tocopherol esters of Example 1                                                                0.1     g                                              jojoba oil 2 g                                                                sesame oil 3 g                                                                vitamin A in palmitate form 0.01 g                                            glycerol 2 g                                                                  water + preservative + surfactant + scent qsp 100 g                         ______________________________________                                    

The cream was prepared as follows. The tocopherol esters were initiallydissolved in the jojoba oil and the sesame oil mixed together, and thenthe palmitate of vitamin A and the glycerol were added, and finally theaqueous phase with the surfactant system was added and the mixturestirred until it was homogenous.

This produced a cream which, when applied in the evening for severalweeks, refined skin grain, gave a luminous complexion, and countered theappearance of wrinkles.

EXAMPLE 5 Anti-Aging Composition in the Form of an Emulsion

    ______________________________________                                        The composition was prepared from the following active ingredients:           ______________________________________                                        the mixture of tocopherol 2,5-dihydroxybenzoate diesters                                                 0.025   g                                            prepared in Example 2                                                         stearates of polyethylene glycol 6 and polyethyleneglycol 15 g                32 as commercially available under the trade                                  reference TEFOSE 63 ®                                                     cetyl palmitate 3 g                                                           cetyl alcohol 3 g                                                             2-hexyl-1-dodecanol 5 g                                                       glycerin 3 g                                                                  2% Carbopol 980 ® gel 5 g                                                 purified water + preservative + scent qsp 100 g                             ______________________________________                                    

To prepare the emulsion, the mixture of tocopherol 2,5-dihydroxybenzoatediesters was initially mixed with the fatty phase until it had beencompletely dissolved, said fatty phase being constituted by theglycerin, the stearates of polyethyleneglycol, the cetyl palmitate, thecetyl alcohol, and the octyldodecanol. Thereafter the purified water wasadded under stirring to form an emulsion, and the carbopol gel was addedto gel the emulsion.

An emulsion- or cream-forming composition was obtained that was appliedlocally for several weeks as an anti-aging care cream.

EXAMPLE 6 Composition in the Form of a Dermatological Lotion

    ______________________________________                                        The dermatological composition was obtained from the following                  active ingredients:                                                         ______________________________________                                        the mixture of tocopherol 2,5-dihydroxybenzoate diesters                                                 0.5     g                                            as obtained in Example 2                                                      absolute ethanol 35 g                                                         scented purified water qsp 100 g                                            ______________________________________                                    

The composition was prepared by initially mixing the diesters in theabsolute ethanol, after which the purified water was added understirring so as to constitute said lotion.

The lotion as applied on the skin presented anti-aging action, refinedskin grain, and gave it a luminous complexion.

What is claimed is:
 1. Esters, characterized in that they present thefollowing chemical formula (I): ##STR14## in which: R₁, R₂ and R₃independently represent an atom of hydrogen, a methyl radical,Arepresents the following groups: ##STR15## R₄ and R₅ are identical ordifferent and each represents a chain of the form:

    --B.sub.m --C.sub.n --B.sub.p --C.sub.q --H

in which: B is the following group: ##STR16## C is the following group:##STR17## and in which the indices m, n, p, and q are respectiveintegers lying in the range 0 to 4, it being understood that the summ+n+p+q is limited to integers in the range 0 to
 4. 2. Esters accordingto claim 1, characterized in that R₄ and R₅ represent hydrogen. 3.Esters according to claim 1, characterized in that at least one of thegroups R₄ and R₅ represents hydrogen.
 4. Esters according to claim 3,characterized in that one of the groups R₄ or R₅ represents hydrogen,and the other a 2,5-dihydroxybenzoyl radical.
 5. Esters according toclaim 1, characterized in that they are selected from the groupconsisting in esters of alpha-tocopherol, of beta-tocopherol, ofgamma-tocopherol, of zeta 1-tocopherol, of zeta 2-tocopherol, ofdelta-tocopherol, of eta-tocopherol, of epsilon-tocopherol, and oftocol.
 6. An ester satisfying following formula (II): ##STR18##
 7. Acomposition selected from the group consisting of a cosmetic and apharmaceutical composition comprising as an active ingredient at leastone ester as defined in claim 1, optionally in a cosmetically orpharmaceutically acceptable excipient.
 8. The composition of claim 7,comprising as an active ingredient at least two esters defined in claim1, in the form of a mixture.
 9. The composition of claim 7, having afatty phase comprising at least one cosmetically or pharmaceuticallyacceptable oil selected from the group consisting of jojoba oil,macadamia oil, limnanthes seed oil, a mineral oil, a triglyceride, andmixtures thereof.
 10. The composition of claim 9, wherein saidlimnanthes seed oil is Limnanthes alba benth seed oil; saidtriglycerides comprising an acid selected from caprylic acid, capricacid and mixtures thereof.
 11. The composition of claim 7, wherein theester concentration ranges between 0.001% and 5% by weight relative tothe total weight of the final composition.
 12. The composition of claim7, wherein the ester concentration ranges between 0.1% and 5% by weightwith respect to the total weight of the final composition.
 13. Thecomposition of claim 7, wherein the ester concentration ranges between0.1% and 1% by weight relative to the total weight of the finalcomposition.
 14. The composition of claim 7, comprising as an activeingredient at least one alpha-tocopherol ester of chemical formula I asdefined in claim 1, in which each of R₁, R₂ and R₃ represents a methylradical and A represents the group: and R₄ and R₅ are as defined inclaim
 1. 15. The composition of claim 7, further comprising at least oneother active ingredient selected from the group consisting of a vitamin,retinoic acid, retinal, retinol, a retinoic acid ester, a retinal ester,a retinol ester, salicylic acid, a salicylic acid salt, a salicylic acidester, 2,5-dihydroxybenzoic acid, tocopherol, a tocopherol ester,asiatic acid, madecassic acid, an ester of asiatic acid with aglycoside, an ester of madecassic acid with a glycoside, asiaticoside,an extract of Centella asiatica, an extract of Siegesbeckia orientalis,a proantocyanide oligomer, an ester of proantocyanide oligomer, a saltof ascorbic acid, ascorbic phosphate, erythorbic acid, a trace element,a trace element salt, an alpha-hydroxylated acid, an ester ofalpha-hydroxylated acid, an amino acid, an amino acid constituting NMF,a ceramide, a photoceramide, an ecdysteroid, an ecdysteroid ester, andmixtures thereof.
 16. The composition of claim 7, wherein said ester isused in admixture with vitamin A or an ester of vitamin A.
 17. Thecomposition of claim 16, wherein said vitamin A ester is vitamin Apalmitate.
 18. A method of cosmetic skin care comprising deliveringtopically to the skin of a human being a cosmetically effective amountof at least one ester as defined in claim
 1. 19. A method of cosmeticcare for performing a cosmetic care selected from the group consistingof avoiding or lowering the harmful effects of free radicals on theskin, for slowing down or eliminating rashes or sensations of skinprickling or stinging, of favoring keratinocyte differentiation, ofrestoring normal moisturizing of the epidermis, of improving skin grainfineness, of slowing down or treating the effects of aging on the skin,of attenuating hyperpigmentation, comprising delivering topically toskin areas of a human being in need thereof, of a cosmetically effectiveamount of at least one ester defined in claim
 1. 20. The cosmetic methodof claim 19, wherein said ester is present in a composition containingsaid ester at a concentration ranging between 0.001% and 5% by weight ofthe final composition.
 21. A method of performing a therapeutictreatment of a human being in need thereof, said therapeutic treatmentbeing selected from the group consisting of counteracting free radicals,counteracting skin inflammation, having an anesthetic action oncutaneous nerve endings of the skin, comprising topically delivering toskin areas of said human being in need thereof, of a therapeuticallyeffective amount of an ester as defined in claim
 1. 22. The method ofclaim 21, wherein said ester is present in a pharmaceutical compositionat a concentration ranging between 0.001% and 5% by weight of the finaltherapeutic composition.